The objectives of this research are to determine: 1) the nature and mechanism of action of suppressor cells which regulate the induction of experimental autoimmune thyroiditis (EAT) in guinea pigs and 2) the basis for the genetic difference in susceptibility to EAT of Strain 2 and Strain 13 guinea pigs. Within the scope of these general objectives these studies will also be aimed at further elucidation of the cellular requirements and mechanisms involved in the pathogenesis of EAT, in the guinea pig. Suppressor cells will be induced by pretreatment with guinea pig thyroglobulin (GPTG) in incomplete Freund's adjuvant, by pretreatment with GPTG coupled to autologous spleen cells or by in vitro incubation of lymphoid cells with GPTG. T cells and B cells from these treated animals will be purified by anti-immunoglobulin fractionation of lymph node cells and will be transferred to normal syngeneic recipients. The suppressor cells will also be characterized with respect to their sensitivity to irradiation, cyclophosphamide, neonatal thymectomy and anti-Ia sera. Anti-immunoglobulin fractionated cells from GPTG-sensitized donors will be used to determine the cell type necessary for transfer of EAT to normal recipients. Strain 2 and Strain 13 guinea pigs will be compared with respect to 1) development of suppressor cells after immunization, 2) development of antigen-specific T cells which proliierate in vitro in the presence of GPTG, 3) activity of lymphoid cells and/or antibody dependent cellular cytotoxicity (ADCC), 4) activity of T cells and/or antibody in direct cytotoxicity of thyroid cells and 5) development of EAT after neonatal thymectomy.